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Jacobs S.E.,Neonatal Services | Jacobs S.E.,Critical Care and Neurosciences Group | Tobin J.M.,North West Academic Center | Opie G.F.,Mercy Hospital for Women | And 8 more authors.
Pediatrics | Year: 2013

BACKGROUND AND OBJECTIVE: Late-onset sepsis frequently complicates prematurity, contributing to morbidity and mortality. Probiotics may reduce mortality and necrotizing enterocolitis (NEC) in preterm infants, with unclear effect on late-onset sepsis. This study aimed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis. METHODS: A prospective multicenter, double-blinded, placebocontrolled, randomized trial compared daily administration of a probiotic combination (Bifidobacterium infantis, Streptococcus thermophilus, and Bifidobacterium lactis, containing 1 3 109 total organisms) with placebo (maltodextrin) in infants born before 32 completed weeks' gestation weighing ,1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis. RESULTS: Between October 2007 and November 2011, 1099 very preterm infants from Australia and New Zealand were randomized. Rates of definite late-onset sepsis (16.2%), NEC of Bell stage 2 or more (4.4%), and mortality (5.1%) were low in controls, with high breast milk feeding rates (96.9%). No significant difference in definite late-onset sepsis or all-cause mortality was found, but this probiotic combination reduced NEC of Bell stage 2 or more (2.0% versus 4.4%; relative risk 0.46, 95% confidence interval 0.23 to 0.93, P = .03; number needed to treat 43, 95% confidence interval 23 to 333). CONCLUSIONS: The probiotics B infantis, S thermophilus, and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants, but not definite late-onset sepsis or mortality. Treatment with this combination of probiotics appears to be safe. Pediatrics 2013;132:1055- 1062. © 2013 by the American Academy of Pediatrics.


Patton G.C.,University of Melbourne | Patton G.C.,Murdoch Childrens Research Institute | Coffey C.,University of Melbourne | Coffey C.,Murdoch Childrens Research Institute | And 9 more authors.
The Lancet | Year: 2014

Background Most adults with common mental disorders report their first symptoms before 24 years of age. Although adolescent anxiety and depression are frequent, little clarity exists about which syndromes persist into adulthood or resolve before then. In this report, we aim to describe the patterns and predictors of persistence into adulthood. Methods We recruited a stratified, random sample of 1943 adolescents from 44 secondary schools across the state of Victoria, Australia. Between August, 1992, and January, 2008, we assessed common mental disorder at five points in adolescence and three in young adulthood, commencing at a mean age of 15·5 years and ending at a mean age of 29·1 years. Adolescent disorders were defined on the Revised Clinical Interview Schedule (CIS-R) at five adolescent measurement points, with a primary cutoff score of 12 or higher representing a level at which a family doctor would be concerned. Secondary analyses addressed more severe disorders at a cutoff of 18 or higher. Findings 236 of 821 (29%; 95% CI 25-32) male participants and 498 of 929 (54%; 51-57) female participants reported high symptoms on the CIS-R (=12) at least once during adolescence. Almost 60% (434/734) went on to report a further episode as a young adult. However, for adolescents with one episode of less than 6 months duration, just over half had no further common mental health disorder as a young adult. Longer duration of mental health disorders in adolescence was the strongest predictor of clear-cut young adult disorder (odds ratio [OR] for persistent young adult disorder vs none 3·16, 95% CI 1·86-5·37). Girls (2·12, 1·29-3·48) and adolescents with a background of parental separation or divorce (1·62, 1·03-2·53) also had a greater likelihood of having ongoing disorder into young adulthood than did those without such a background. Rates of adolescent onset disorder dropped sharply by the late 20s (0·57, 0·45-0·73), suggesting a further resolution for many patients whose symptoms had persisted into the early 20s. Interpretation Episodes of adolescent mental disorder often precede mental disorders in young adults. However, many such disorders, especially when brief in duration, are limited to the teenage years, with further symptom remission common in the late 20s. The resolution of many adolescent disorders gives reason for optimism that interventions that shorten the duration of episodes could prevent much morbidity later in life. Copyright © Chatterjee et al.


Gunn J.K.,University of Melbourne | Donath S.M.,Clinical Epidemiology and Biostatistics Unit | Donath S.M.,University of Melbourne | Donath S.M.,Murdoch Childrens Research Institute | And 3 more authors.
Pediatrics | Year: 2010

CONTEXT: Brain injury is the most common long-term complication of congenital heart disease requiring surgery during infancy. It is clear that the youngest patients undergoing cardiac surgery, primarily neo-nates and young infants, are at the greatest risk for brain injury. Develop-mental anomalies sustained early in life have lifelong repercussions. OBJECTIVE: We conducted a systematic reviewto examine longitudinal studies of cognitive and/or motor outcome after cardiac surgery dur-ing early infancy. METHODS: Electronic searches were performed in Medline, the Cumu-lative Index to Nursing and Allied Health Literature (Cinahl), and Em-base (1998-2008). The search strategy yielded 327 articles, of which 65 were reviewed. Eight cohorts provided prospective data regarding the cognitive and/or motor outcome of infants who had undergone surgery for congenital heart disease before 6 months of age. Two authors, Ms Snookes and Dr Gunn, independently extracted data and presented results according to 3 subgroups for age of follow-up: early develop-ment (1 to <3 years); preschool age (3-5 years); and school age (>5 to 17 years). Weighted analysis was undertaken to pool the results of studies when appropriate. RESULTS: All of the identified studies reported results of the Bayley Scales of Infant Development for children younger than the age of 3. Outcome data as reported by the Bayley Scales were combined for infants assessed at 1 year of age, revealing a weighted mean Mental Development Index of 90.3 (95% confidence interval: 88.9-91.6) and Psychomotor Development Index of 78.1 (95% confidence interval: 76.4-79.7). Additional analysis was limited by a lack of data at pre-school and school age. CONCLUSIONS: With this review we identified a limited number of pro-spective studies that systematically addressed outcome in patients at the highest risk. These studies consistently revealed cognitive and mo-tor delay in children after cardiac surgery during early infancy. Addi-tional investigation is required to ascertain the consequences of such impairment during later childhood and into adult life.


Patton G.C.,Royal Childrens Hospital | Patton G.C.,Murdoch Childrens Research Institute | Patton G.C.,University of Melbourne | Tollit M.M.,Royal Childrens Hospital | And 9 more authors.
Pediatrics | Year: 2011

CONTEXT: The promotion of optimism has been widely advocated for children and adolescents, but epidemiologic data to support this approach are scant. METHODS: This was a 3-wave longitudinal study of health and social development in younger adolescents from 3 Australian states. The 5634 student participants, initially aged 12 to 14 years, were assessed for optimistic thinking style, emotional problems, substance use, and antisocial behaviors. RESULTS: Cross-sectional associations between optimism and each of the study outcomes were strongly protective but tended to differ according to gender in extent. In prospective analyses of the onset of new cases of each study outcome, protective associations were weaker. Those in the highest optimism quartile had risks for depressive symptoms that were reduced by almost half (odds ratio: 0.54 [95% confidence interval: 0.42-0.70]) compared with those in the lowest category. No effect was seen in prevention of anxiety symptoms after adjustment for other aspects of psychological style. In predicting the onset of heavy substance use and antisocial behavior, high optimism had modest protective effects. CONCLUSIONS: Optimistic thinking style is somewhat protective against adolescent health risks; the clearest effects are seen against depressive symptoms. Promoting optimism along with other aspects of psychological and emotional style has a role in mental health promotion that is likely to be enhanced if an intervention also addresses risk and protective factors in an adolescent's social context. Copyright © 2011 by the American Academy of Pediatrics.


Del Fante C.,Apheresis and Cell Therapy Unit | Scudeller L.,Clinical Epidemiology and Biostatistics Unit | Martinasso A.,Apheresis and Cell Therapy Unit | Viarengo G.,Apheresis and Cell Therapy Unit | Perotti C.,Apheresis and Cell Therapy Unit
Transfusion | Year: 2016

BACKGROUND: Extracorporeal photopheresis (ECP) is an effective cell therapy employed in several diseases, including graft versus host disease (GVHD) and organ rejection. When ECP is performed using an off-line technique, mononuclear cell (MNC) collection by leukapheresis is necessary for further manipulation (addition of 8-methoxypsoralen and ultraviolet A irradiation before reinfusion to the patient). We report the results of the first crossover equivalence study on yield and purity of MNCs collected from patients undergoing ECP with two different automated systems: MNC and CMNC (working with intermittent and continuous-flow collection, respectively), released by Terumo BCT. STUDY DESIGN AND METHODS: Fifty-one patients (15 males and 36 females) with GVHD or chronic lung allograft dysfunction were consecutively enrolled and randomly assigned to MNC collection alternatively by the CMNC or MNC system within each ECP cycle (two procedures) in two consecutive cycles. ECP procedures were performed using the off-line technique, according to our internal protocol, processing 1.5 blood volumes. RESULTS: A total of 204 ECP procedures were evaluated. The MNC system showed a higher MNC concentration capacity than the CMNC (mean difference, −13.46; 95% confidence interval, −21.05 to −5.47; p < 0.001). Collection efficiency was higher with the CMNC system as well as total MNC bag content, while MNC bag purity was equivalent for both systems. Platelet loss was higher with the CMNC. Equivalence was shown for MNC purity and anticoagulant infused to the patient. CONCLUSION: CMNC and MNC systems offer different advantages in different clinical conditions, and both are safe and efficient in collecting MNCs for ECP. © 2016 AABB


Ferreiro A.O.,University of La Coruña | Vazquez-Millan M.A.,University of La Coruña | Lopez F.S.,University of La Coruña | Gutierrez M.G.,University of La Coruña | And 2 more authors.
Transplantation Proceedings | Year: 2014

Background. Liver transplantation offers the most effective treatment in patients with hepatocellular carcinoma (HCC).However, transplant patients outside the Milan criteria have a high risk of tumor recurrence, which has been linked to standard immunosuppression regimens. Everolimus is a mammalian target of rapamycin inhibitor that has been used for immunosuppression, but its effect on recurrence and survival in HCC patients with a high risk of tumor recurrence has not been examined. We compared long-termsurvival and cumulative recurrence in high-risk patients receiving everolimus-based immunosuppression after liver transplantation for HCC with an historic control group. Methods. The everolimus group comprised 21 patients receiving a liver transplant at our center from February 2005 to December 2010. The control group comprised 31 patients receiving a liver transplant fromMay 1994 to January 2005. All patients received cyclosporine or tacrolimus as initial post-transplant immunosuppression. Patients in the everolimus group switched to everolimus 2 weeks later. Results. There were no differences between the two groups in number of rejection episodes or of infectious or surgical complications. Five-year survival was 60.2%in the everolimus group and 32.3% in the control group (P = .05). Five-year cumulative recurrence rate was 61.3% in the control group and 41.3% in the everolimus group. Treatment with everolimus was identified as an independent predictor of longer survival (hazard ratio = 0.34; P = .02). Conclusions. Patients receiving liver transplantation for HCC with a high risk of tumor recurrence may well benefit from everolimus-based immunosuppression, with no added risks of rejection or other post-transplant complications.


Lean W.L.,Royal Melbourne Hospital | Arnup S.,Clinical Epidemiology and Biostatistics Unit | Danchin M.,Royal Melbourne Hospital | Steer A.C.,Royal Melbourne Hospital
Pediatrics | Year: 2014

BACKGROUND AND OBJECTIVE: Effective management of group A streptococcal (GAS) pharyngitis is hindered by impracticality of the gold standard diagnostic test: throat culture. Rapid antigen diagnostic tests (RADTs) are a promising alternative, although concerns about their sensitivity and specificity, and variation between test methodologies, have limited their clinical use. The objective of this study was to perform a systematic review with meta-analysis of the diagnostic accuracy of RADTs for GAS pharyngitis.METHODS: Medline and Embase from 1996 to 2013 were used as data sources. Of 159 identified studies, 48 studies of diagnostic accuracy of GAS RADTs using throat culture on blood agar as a reference standard were selected. Bivariate random-effects regression was used to estimate sensitivity and specificity with 95% confidence intervals (CIs). Additional meta-analyses were performed for pediatric data.RESULTS: A total of 60 pairs of sensitivity and specificity from 48 studies were included. Overall summary estimates for sensitivity and specificity of RADTs were 0.86 (95% CI 0.83 to 0.88) and 0.96 (95% CI 0.94 to 0.97), respectively, and estimates for pediatric data were similar. Molecular-based RADTs had the best diagnostic accuracy. Considerable variability exists in methodology between studies. There were insufficient studies to allow meta-regression/subgroup analysis within each test type.CONCLUSIONS: RADTs can be used for accurate diagnosis of GAS pharyngitis to streamline management of sore throat in primary care. RADTs may not require culture backup for negative tests in most low-incidence rheumatic fever settings. Newer molecular tests have the highest sensitivity, but are not true point-of-care tests. Copyright © 2014 by the American Academy of Pediatrics.


Novakovic B.,Murdoch Childrens Research Institute | Novakovic B.,University of Melbourne | Galati J.C.,Clinical Epidemiology and Biostatistics Unit | Chen A.,Murdoch Childrens Research Institute | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2012

Background: There are multiple potential regulators of neonatal vitamin D status of environmental, genetic, and epigenetic origins. The relation between these factors and circulating neonatal vitamin D has yet to be fully characterized. Objective: The aim of this study was to examine the relative contribution of genetic factors, maternal circulating 25-hydroxyvitamin D [25(OH)D] concentrations, and the placental methylation level of the gene that encodes the primary catabolic enzyme of active vitamin D [25(OH)D-24-hydroxylase encoded by CYP24A1] to neonatal 25(OH)D concentrations. Design: We used the classical twin study design to determine the genetic contribution to neonatal 25(OH)D. A total of 86 twin pairs (32 monozygotic and 54 dizygotic twin pairs) were included in this study. Serum 25(OH)D was measured by using a 25(OH)D kit. CYP24A1 promoter DNA methylation was measured by means of matrix-assisted laser desorption time-of-flight mass spectrometry. Results: Maternal and neonatal 25(OH)D showed a strong association (R2 = 0.19). Monozygotic and dizygotic within-pair serum 25(OH)D correlations were similar (R2 = 0.71 and 0.67, respectively), which suggested no genetic effect. Placental CYP24A1 methylation did not show an association with maternal or neonatal 25(OH)D concentrations. Conclusions: Our results suggest that maternal circulating 25(OH)D is the most significant regulator of neonatal circulating 25(OH)D concentrations, with underlying genetic factors playing a limited role. The placental methylation of the CYP24A1 promoter appears subject to a genetic influence, although no evidence of a relation between the methylation level of this gene and circulating maternal or neonatal 25(OH)D was apparent. © 2012 American Society for Nutrition.


PubMed | Clinical Epidemiology and Biostatistics Unit and Apheresis and Cell Therapy Unit
Type: Journal Article | Journal: Transfusion | Year: 2016

Extracorporeal photopheresis (ECP) is an effective cell therapy employed in several diseases, including graft versus host disease (GVHD) and organ rejection. When ECP is performed using an off-line technique, mononuclear cell (MNC) collection by leukapheresis is necessary for further manipulation (addition of 8-methoxypsoralen and ultraviolet A irradiation before reinfusion to the patient). We report the results of the first crossover equivalence study on yield and purity of MNCs collected from patients undergoing ECP with two different automated systems: MNC and CMNC (working with intermittent and continuous-flow collection, respectively), released by Terumo BCT.Fifty-one patients (15 males and 36 females) with GVHD or chronic lung allograft dysfunction were consecutively enrolled and randomly assigned to MNC collection alternatively by the CMNC or MNC system within each ECP cycle (two procedures) in two consecutive cycles. ECP procedures were performed using the off-line technique, according to our internal protocol, processing 1.5 blood volumes.A total of 204 ECP procedures were evaluated. The MNC system showed a higher MNC concentration capacity than the CMNC (mean difference, -13.46; 95% confidence interval, -21.05 to -5.47; p<0.001). Collection efficiency was higher with the CMNC system as well as total MNC bag content, while MNC bag purity was equivalent for both systems. Platelet loss was higher with the CMNC. Equivalence was shown for MNC purity and anticoagulant infused to the patient.CMNC and MNC systems offer different advantages in different clinical conditions, and both are safe and efficient in collecting MNCs for ECP.


PubMed | Clinical Epidemiology and Biostatistics Unit, University of Udine, University of Bologna and Azienda Ospedaliero Universitaria Santa Maria della Misericordia
Type: Journal Article | Journal: The Annals of pharmacotherapy | Year: 2015

Prompt administration of antibiotics, adjunctive steroid therapy, and optimization of antibiotic delivery to cerebrospinal fluid (CSF) are factors associated with improved outcome of patients hospitalized for acute bacterial meningitis (ABM). However, the impact of a bundle of these procedures has not been reported.To assess mortality and neurological sequelae at hospital discharge in a cohort of patients with ABM managed according to a predefined bundle.Prospective study of all the patients hospitalized for ABM in two provinces of Northern Italy, over two consecutive periods (2005-2009, 2010-2013). The bundle included: i) supportive care if needed; ii) immediate administration of dexamethasone and 3rd generation cephalosporin; and iii) addition of levofloxacin if turbid CSF. Patients managed according to the bundle were compared with a historical group of patients cared for ABM before the bundle was implemented.Overall, 85 patients with ABM were managed according to the bundle and were compared with 92 historical controls. In-hospital mortality rates for bundle and control group were 4.7% and 14.1% (p=0.04). Among survivors, 13.5% and 18.9% (p=0.4) of bundle and control-group patients presented neurological sequelae. The only variable associated with mortality at multivariate analysis was ICU admission (HR 3.65). After adjusting for ICU admission, patients managed according with the ABM bundle had significantly lower mortality rate compared to historical controls.Use of a bundled protocol and antibiotics with excellent CSF penetration for the initial management of ABM in emergency department is feasible and associated with significant reduction in mortality.

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